Insulin Secretion (Oral Glucose Tolerance Test Sample Clauses

Insulin Secretion (Oral Glucose Tolerance Test. Cystic fibrosis related diabetes (CFRD) is characterized by progressive insulin insufficiency. It is extraordinarily prevalent in the CF population, occurring in 15-20% of adolescents and, eventually, more than half of adults.59 Few of the remaining patients have completely normal glucose metabolism; even those with normal fasting and 2-hour OGTT glucose levels typically have mid-OGTT glucose elevation (indeterminate glycemia) and have defective acute insulin secretion in response to intravenous glucose.60 While CFRD does not usually develop before puberty, it has its roots in childhood and glucose intolerance is common in 6-9 year old children with CF.61 In childhood, CF patients are able to compensate for this defect because their beta-cell mass is largely intact. As islets are lost over time due to exocrine fibrosis and as chronic, unrelenting beta-cell stress occurs due to inflammation, oxidative stress and recurrent infection, the impact of CFTR on insulin secretion becomes more critical. We postulate that CFTR plays a small but important role in insulin secretion. A pilot study in five CF patients with the G551D CFTR mutation that measured insulin secretion before and 1 month after initiation of ivacaftor therapy provided preliminary evidence that drugs that improve CFTR function may increase insulin secretion in CF. After 1 month of ivacaftor therapy, the insulin response to oral glucose improved by 66-178% in all subjects except the one with long standing diabetes (p=0.07). While childhood may be the ideal time to intervene (with the hope of establishing a healthy “bank” of fully functional beta cells which are better able to withstand the metabolic stresses of CF that escalate over time) further data needs to be gathered in adults before studying children. Longitudinal assessment of a greater number of subjects with CF is necessary to determine whether early correction of CFTR could delay or even prevent diabetes. Oral glucose tolerance testing will be performed in a subset of subjects enrolled in the Part B CORE study to examine the role of CFTR in human insulin secretion, potentially opening the way for novel diabetes therapies and for prevention or at least amelioration of diabetes in CF.
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